Mercolini Laura, Colliva Carolina, Amore Mario, Fanali Salvatore, Raggi Maria Augusta
Laboratory of Pharmaco-Toxicological Analysis, Department of Pharmaceutical Sciences, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
J Pharm Biomed Anal. 2008 Aug 5;47(4-5):882-7. doi: 10.1016/j.jpba.2008.02.028. Epub 2008 Mar 4.
The present paper deals with the development of a rapid and feasible high-performance liquid chromatographic method for the determination of trazodone and its main active metabolite 3-(1-clorophenyl)piperazine (m-CPP) in human plasma. Trazodone is a second-generation antidepressant with serotonin antagonist activity. The metabolite seems to be involved in the onset of some side effects of trazodone therapy, thus its determination is very important during therapeutic drug monitoring. Separation was achieved using a C8 reversed-phase column and a mobile phase composed of aqueous phosphate buffer (70%), containing triethylamine, at pH 3.5 and acetonitrile (30%). The UV detector was set at 255 nm and loxapine was used as the internal standard. An original pre-treatment procedure of plasma samples was developed, based on solid-phase extraction with C8 reversed phase cartridges (50mg, 1 mL). The obtained extraction yields values were higher than 90% and precision, expressed as R.S.D., was lower than 5.6%. The method was successfully applied to plasma samples from depressed patients undergoing therapy with trazodone; accuracy results were satisfactory (recovery >91%). Thus, the method seems to be suitable for the therapeutic drug monitoring of trazodone and its main active metabolite in depressed patients' plasma.
本文论述了一种快速可行的高效液相色谱法的开发，用于测定人血浆中的曲唑酮及其主要活性代谢物3-(1-氯苯基)哌嗪(m-CPP)。曲唑酮是一种具有5-羟色胺拮抗剂活性的第二代抗抑郁药。该代谢物似乎与曲唑酮治疗的某些副作用的发生有关，因此在治疗药物监测期间对其进行测定非常重要。使用C8反相柱和由pH值为3.5的含三乙胺的磷酸盐缓冲水溶液(70%)和乙腈(30%)组成的流动相实现分离。紫外检测器设定在255nm，洛沙平用作内标。基于用C8反相柱(50mg，1mL)进行固相萃取，开发了一种原始的血浆样品预处理程序。获得的萃取产率值高于90%，以相对标准偏差表示的精密度低于5.6%。该方法已成功应用于接受曲唑酮治疗的抑郁症患者的血浆样品；准确度结果令人满意(回收率>91%)。因此，该方法似乎适用于抑郁症患者血浆中曲唑酮及其主要活性代谢物的治疗药物监测。
